This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Visual signaling is an accessible paradigm while of extreme importance in understanding vision and blinding diseases is also an accessible paradigm for the understanding of the macromolecular machinery that underlies all G protein coupled receptor signaling events. We utilize photoactivated rhodopsin and complexes thereof to probe photostates of rhodopsin that are analogous to activated states of GPCRs through a combination of biochemistry, biophysics and structural study. RPE65 is the isomerase responsible for the regeneration of the chromophore necessary for vision and has been implicated in several human blinding disorders. Through work performed at NECAT as well as at X29 at BNL we solved the first structure of this protein in 2009.